This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Integrity of the periodontal ligament (PDL) is imperative for oral health. Periodontal disease typified by inflammatory degradation of this collagen-rich tissue can lead to loss of gingival adhesion and eventual tooth loss. In addition, periodontal disease is frequently associated with cardiovascular disease, diabetes, and preterm births. Hence, an active area of oral health research is the characterization of factors important for the maintenance and repair of collagen in the PDL. SPARC is a secreted collagen-binding protein with counter-adhesive and anti-proliferative activity. SPARC is required for efficient collagen deposition and stable accumulation as established by virtue of transgenic mice that do not express SPARC that exhibit significant decreases in amounts of collagen in tissues. We have demonstrated a similar reduction in collagen in the PDL of SPARC-null mice. We hypothesize that SPARC functions to bind collagen I and thereby diminish collagen interaction with cell-surface receptors that allows for stable incorporation of collagen I into the extracellular matrix (ECM). In the absence of SPARC, we predict that collagen produced by PDL fibroblasts exhibits increased engagement of collagen receptors leading to rapid internalization of collagen at the expense of ECM deposition. Therefore, SPARC is implicated as a key regulator of collagen turnover. As PDL exhibits one of the highest rates of collagen turnover in the body, this tissue is an ideal milieu in which to characterize SPARC function. In Aim 1 of this proposal, we will characterize the effects on collagen I deposition in the PDL in the absence of SPARC in vivo over time. Experiments outlined in Aim 2 will determine whether SPARC expression reduces collagen uptake by PDL fibroblasts in vitro and whether this uptake is dependent upon integrin [unreadable]2[unreadable]1 receptor. Aim 3 explores whether increased expression of SPARC associated with aging contributes to reduced collagen turnover and lower rates of proliferation indicative of fibroblasts from aged PDL. Completion of these Specific Aims will provide a solid foundation on which to build a productive line of research into a critical element that preserves and maintains collagen structural integrity of the PDL.